Winrevair (sotatercept-csrk) for pulmonary arterial hypertension

Last updated Sept. 3, 2024, by Marisa Wexler, MS
Fact-checked by Inês Martins, PhD

What is Winrevair for pulmonary hypertension?

Winrevair (sotatercept-csrk) is an injection therapy approved in the U.S. for adults with pulmonary arterial hypertension (PAH). It is designed to improve exercise capacity and World Health Organization (WHO) functional class, and to reduce the risk of disease-related clinical problems.

Sold by Merck, the therapy is administered via subcutaneous, or under-the-skin, injections.

Therapy snapshot

How does Winrevair work?

PAH is marked by increased pressure in the blood vessels that carry blood from the heart to the lungs. This is due to the abnormal growth of the endothelial cells that line the inside of these blood vessels, causing them to become narrower, and driving disease progression.

Cell growth is controlled by signaling molecules called growth factors. A particular class of growth factors, called the transforming growth factor beta (TGF-beta) superfamily, plays a central role in driving the abnormal growth of endothelial cells in PAH.

The active agent in Winrevair is essentially a fragment of a growth factor receptor that’s designed to act as a trap for molecules belonging to this superfamily. By binding to these molecules, the therapy prevents them from sending signals to cells, which is expected to lessen the abnormal growth of blood vessel cells that drives disease progression in PAH.

Who can use Winrevair?

Winrevair was approved by the U.S. Food and Drug Administration (FDA) in March 2024 to treat adults with PAH. It was the first treatment in its class to receive approval from the regulatory agency for this indication. The therapy is specifically indicated to increase exercise capacity, improve WHO functional class, and reduce the risk of clinical worsening events.

Soon after, Winrevair was approved in the European Union, as well as in Iceland, Liechtenstein, and Norway, to be used in combination with other PAH therapies to improve exercise capacity in PAH patients with WHO functional class 2 or 3, meaning the disease limits their physical activity, but patients are comfortable when at rest.

Who should not use Winrevair?

The prescribing information for Winrevair does not list any contraindications.

However, the medication should not be started in patients with platelet counts lower than 50,000 per cubic millimeter. Platelets are small cell fragments in the blood that form clots and stop or prevent bleeding.

It also is not recommended for use during breastfeeding.

How is Winrevair administered?

Winrevair is given every three weeks via subcutaneous injection in the stomach or upper thigh. Injections should initially be administered under the guidance of a healthcare professional, but with proper training, patients or caregivers may administer the medication in the comfort of their own homes.

The medication is available in single-use vials containing either 45 or 60 mg of the active therapy as an off-white powder or cake, which should be reconstituted in sterile water for a final concentration of 50 mg of the medication for every 1 mL of solution.

Winrevair is dosed according to the patient’s body weight as measured in kilograms. For the first injection of Winrevair, the recommended dosage is 0.3 mg/kg. After that first dose, patients should undergo blood tests to monitor for adverse reactions. If blood findings are stable, subsequent injections are given at a target dose of 0.7 mg/kg.

If patients show certain blood abnormalities while on Winrevair, scheduled injections should be delayed for at least three weeks to allow those values to normalize. The blood abnormalities are:

• hemoglobin levels that increase by more than 2 g/dL from the prior dose and are above the normal range
• hemoglobin levels that are more than 2 g/dL above the normal range
• hemoglobin that has increased more than 4 g/dL since starting on Winrevair
• platelet counts that are lower than 50,000 per cubic millimeter.

These patients should be tested before restarting Winrevair; if the treatment delay lasts more than nine weeks, treatment should be restarted at the 0.3 mg/kg dose.

If a scheduled dose of Winrevair is missed, an injection should be given as soon as possible. However, if the new injection is not given within three days of the original schedule, the subsequent dose should be given three weeks after that to maintain the three-week interval between doses.

Winrevair in clinical trials

The approval of Winrevair for PAH was mainly based on data from a Phase 3 clinical trial called STELLAR (NCT04576988), which enrolled 323 adults with PAH.

At the start of the trial, participants were categorized as WHO functional class 2 or 3. More than half had idiopathic PAH, which means the disease does not have a clear cause; the rest included patients with hereditary or connective tissue PAH.

The participants were randomly assigned to receive injections of Winrevair at the now-approved dosing schedule, or a placebo, on top of their standard-of-care PAH treatment for about six months. Those who completed this part could then join an open-label extension, in which all were treated with Winrevair for as long as 1.5 years.

The study’s main goal was to assess the impact of treatment on the distance participants could walk in six minutes, which is a common measure used to assess exercise capacity in people who can walk.

The results after six months showed Winrevair significantly increased the distance walked in six minutes by 40.8 meters (about 134 feet) compared with a placebo.

A significantly greater percentage of patients on Winrevair (29% vs. 14%) also experienced an improvement in WHO functional class during the placebo-controlled part of the study. Markers of heart health and blood flow similarly improved with Winrevair relative to the placebo.

Over a median follow-up time of more than seven months, two participants in the Winrevair group died, and another seven experienced clinical worsening events, such as needing to be listed for a lung and/or heart transplant, or experiencing a substantial worsening in functional class and walking ability. By comparison, in the placebo group, seven patients died and another 35 experienced clinical worsening events. Altogether, that represented an 84% lower risk of experiencing death or any of these events with Winrevair treatment.

Mathematical models based on these short-term data suggested the therapy may improve long-term survival in PAH by 11.5 years, though this still must be definitively proven.

About a quarter of patients given Winrevair developed antibodies against the therapy, although these did not appear to affect the treatment’s efficacy.

Common side effects of Winrevair

The most common side effects of Winrevair include:

• headache
• rash
• nosebleed (epistaxis)
• damaged veins visible under the skin, known as telangiectasias or spider veins
• diarrhea
• dizziness
• skin redness (erythema).

High hemoglobin counts

Winrevair may increase levels of hemoglobin, the protein that red blood cells use to carry oxygen throughout the body. This may cause erythrocytosis, or a high number of red blood cells in circulation, which can increase the risk for clotting or blood flow problems.

Hemoglobin levels should be monitored for at least the first five doses of Winrevair, or longer if values aren’t stable, and they should be checked regularly thereafter. If hemoglobin levels become abnormal, the next scheduled dose of Winrevair should be delayed, as per the therapy’s administration instructions.

Low platelet counts

Winrevair may decrease platelet levels, which can increase a patient’s risk of serious bleeding. Platelet counts should be monitored for at least the first five treatment doses, or longer if levels aren’t stable, and checked periodically thereafter.

Patients should not be started on Winrevair if their platelet counts drop below 50,000 per cubic millimeter. For individuals already on treatment, the next injection should be delayed if platelet levels drop below that level.

Risk of severe bleeding

In clinical studies, severe bleeding occurred in 4% of patients given Winrevair, compared with 1% of those on the placebo. These events were more likely among patients taking prostacyclin and/or anti-clotting medications, or for those who had low platelet counts.

Patients starting on Winrevair should be educated about the potential signs of serious bleeding, and should be treated promptly if a serious bleed occurs. Winrevair should not be administered to anyone who is actively experiencing a serious bleed.

Reduced fertility

Based on animal data, Winrevair may reduce fertility in both male and female patients. It’s not entirely clear if this also affects people or if these effects are reversible, so patients should consider this possible risk when deciding whether or not to start the therapy.

Risk of harm during pregnancy and breastfeeding

In animal studies, the use of Winrevair during pregnancy at doses comparable to the approved dose caused problems with fetal development, including higher rates of fetal death and abnormal growth.

Due to the risk of fetal harm caused by Winrevair, patients with the potential to become pregnant are advised to use effective means of contraception while on treatment and for at least four months after the last dose.

There is no data on whether Winrevair is excreted in human breast milk, but due to a theoretical risk that a breastfeeding infant may experience serious adverse reactions when exposed to the drug, the FDA advised patients should not breastfeed while on Winrevair and for at least four months after the final dose.

If Winrevair is administered during pregnancy or breastfeeding, outcomes may be reported to Merck at 1-877-888-4231.

Pulmonary Hypertension News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.